Phenotype variability in patients carrying KCNJ2 mutations.
Abstract | BACKGROUND: METHODS AND RESULTS: Mutational analyses of KCNJ2 were performed in 57 unrelated probands showing typical (≥2 ATS features) and atypical (only 1 of the ATS features or CPVT) ATS. We identified 24 mutation carriers. Mutation-positive rates were 75% (15/20) in typical ATS, 71% (5/7) in cardiac phenotype alone, 100% (2/2) in periodic paralysis, and 7% (2/28) in CPVT. We divided all carriers (n=45, including family members) into 2 groups: typical ATS (A) (n=21, 47%) and atypical phenotype (B) (n=24, 53%). Patients in (A) had a longer QUc interval [(A): 695 ± 52 versus (B): 643 ± 35 ms] and higher U-wave amplitude (0.24 ± 0.07 versus 0.18 ± 0.08 mV). C-terminal mutations were more frequent in (A) (85% versus 38%, P<0.05). There were no significant differences in incidences of ventricular tachyarrhythmias. Functional analyses of 4 mutations found in (B) revealed that R82Q, R82W, and G144D exerted strong dominant negative suppression (current reduction by 95%, 97%, and 96%, respectively, versus WT at -50 mV) and T305S moderate suppression (reduction by 89%). CONCLUSIONS: KCNJ2 gene screening in atypical ATS phenotypes is of clinical importance because more than half of mutation carriers express atypical phenotypes, despite their arrhythmia severity.
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Authors | Hiromi Kimura, Jun Zhou, Mihoko Kawamura, Hideki Itoh, Yuka Mizusawa, Wei-Guang Ding, Jie Wu, Seiko Ohno, Takeru Makiyama, Akashi Miyamoto, Nobu Naiki, Qi Wang, Yu Xie, Tsugutoshi Suzuki, Shigeru Tateno, Yoshihide Nakamura, Wei-Jin Zang, Makoto Ito, Hiroshi Matsuura, Minoru Horie |
Journal | Circulation. Cardiovascular genetics
(Circ Cardiovasc Genet)
Vol. 5
Issue 3
Pg. 344-53
(Jun 2012)
ISSN: 1942-3268 [Electronic] United States |
PMID | 22589293
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Kir2.1 channel
- Potassium Channels, Inwardly Rectifying
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Topics |
- Adolescent
- Adult
- Andersen Syndrome
(epidemiology, genetics)
- Child
- Child, Preschool
- DNA Mutational Analysis
- Female
- Genotype
- Humans
- Male
- Mutation
- Phenotype
- Polymorphism, Single Nucleotide
- Potassium Channels, Inwardly Rectifying
(analysis, genetics, metabolism)
- Prevalence
- Tachycardia, Ventricular
(epidemiology, genetics)
- Young Adult
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